Evaluation of the central and antinociceptive effects of isolated fractions from the root of Petiveria alliacea L. (tipi) in mice.

by Gomes, Patrícia Bezerra

Abstract (Summary)

Evaluation of the central and antinociceptive effects of isolated fractions from the root of Petiveria alliacea L. (tipi) in mice. PATRÍCIA BEZERRA GOMES. Supervisor: Profa. Dra. Francisca Cléa Florenço de Sousa. Master Dissertation. Course of Post-graduation in Pharmacology. Department of Physiology and Pharmacology, UFC, 2006. Petiveria alliacea L. a shrub from Phytolaccaceae family, is popularly used in folk medicine for treating a wide variety of disorders in South and Central America. The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of tipi were studied to investigate its pharmacological properties in animals nocicepcion models (abdominal contractions induced by acetic acid, formalin 1% and hot plate tests) and in the classical behavioral models (open-field, elevated plus maze- EPM, rota rod, barbiturate-induced sleeping time, forced swimming and pentylenetetrazole (PTZ)-induced convulsions tests). Were analyzed the phytoconstituents presents in it, the general pharmacological effects and acute toxicity. The fractions were administered orally (p.o.) and/or intraperitoneally (i.p.), at single doses of 100 and 200 mg/kg, in female mice. The phytochemical approach of the fractions from Petiveria alliacea demonstrated the presence of alkaloids in FA, coumarins in FA, FHA and FHAppt, saponins and triterpenes in FA, FH, FHA and FHAppt. The hidroalcoholic extract (500, 1000, 1500 and 2000 mg/kg, i.p.; 1000, 2000, 3000 and 4000 mg/kg, p.o.) of the tipi presented a low toxicity and the parameters more visualized were analgesic, decrease in locomotor activity and passive behavior. All the fractions inhibited the abdominal contractions induced by acetic acid. FA (200 mg/kg, i.p.), FH and FHAppt (100 and 200 mg/kg, i.p.), reduced the nocicepcion produced by formalin in the 1st and 2nd phases. FHA (100 and 200 mg/kg, i.p.) presented a significant inhibition on the 1st phase, of this test, indicating a possible antinociceptive effect. The antinociceptive effect produced by FHAppt (200 mg/kg, i.p.) was reversed by naloxone (2 mg/kg, s.c.), showing the participation of the opioid system in this process. No significant effect was observed in the hot plate test. All the fractions of tipi induced a significant decrease in the locomotor activity, rearing and grooming in the open field test, suggesting a possible central depressant action. No significant effect was evident on motor coordination of the animals in the rota rod test. On LCE, FA (100 and 200 mg/kg, p.o.) decreased the NEOA (nº of entries in the open arms) and the TPOA (time of permanence in the open arms). FA, FH and FHA (100 and 200 mg/kg, i.p.), FHAppt (200mg/kg, i.p.) presented a significant reduction of the TPOA, indicating an absence of anxiolytic effect. The fractions from the root of Petiveria alliacea promoted a significant increase in the immobility time of the mice in the forced swimming test. Moreover, corroborating these results, as caused a prolongation of the pentobarbital-induced sleeping time, confirmed a probable sedative and central depressant effect. The neuropharmacological effects of the FHA (200 mg/kg, i.p.), observed in the open field and barbiturate-induced sleeping time tests, weren?t reverted with the administration of the flumazenil (2.5 mg/kg, i.p.), indicating that the mechanism of action of the FHA, probably didn?t related with the participation of the GABAergic receptors. All the fractions of Petiveria alliacea increased the latency to the first convulsion and the lethal time of the PTZ-induced convulsions test in the animals, confirmed its popular use as anticonvulsant. Results showed that the different fractions of Petiveria alliacea L. have significant antinociceptive, sedative, depressant and anticonvulsant potentials, due to presence in this constituents, supporting folk medicine use of this plant.